Lack of cocaine-like discriminative-stimulus effects of σ-receptor agonists in rats

Takato Hiranita, Paul L. Soto, Gianluigi Tanda, Jonathan L. Katz

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Previous studies demonstrated the effectiveness of selective σ-receptor (σR) agonists [1,3-di-o-tolylguanidine (DTG), PRE-084] as reinforcers in rats trained to self-administer cocaine. Similar to cocaine, these drugs increased nucleus accumbens shell dopamine levels, and effects of DTG, but not PRE-084, on dopamine seemed to be mediated by σRs. In addition, σR antagonists blocked self-administration of σR agonists, but were inactive against reinforcing and neurochemical effects of cocaine. Thus, pharmacologically distinct mechanisms likely underlie the reinforcing and neurochemical effects of σR agonists and cocaine. This study further examined the cocaine-like effects of σR agonists in rats trained to discriminate injections of cocaine from saline to assess the similarity of their subjective effects. Standard dopamine-uptake inhibitors (WIN 35 428, methylphenidate), but neither σR agonist (PRE-084, DTG), produced full cocaine-like discriminative-stimulus effects. The lack of effects of σR agonists was obtained regardless of route of administration (intraperitoneal, subcutaneous, or intravenous) or pretreatment time (5 or 30 min before sessions). The present results demonstrate differences in the discriminative-stimulus effects of cocaine and selective σR agonists, indicating that an overlap of subjective effects is not necessary for σR agonist self-administration. The previously found differences in neurochemical effects of cocaine and σR agonists may contribute to their different subjective effects.

Original languageEnglish (US)
Pages (from-to)525-530
Number of pages6
JournalBehavioural pharmacology
Issue number5-6
StatePublished - Sep 2011
Externally publishedYes


  • 1,3-di-o-tolylguanidine
  • PRE-084
  • WIN 35 428
  • cocaine
  • discriminative-stimulus effects
  • dopamine-uptake inhibitor
  • methylphenidate
  • σ receptor

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology


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